[azmanam]

Very fun transformation this week. I've provided the (yes, desired) product of this tandem transformation.

QUESTION: Provide the mechanism and name the two named reactions in this tandem transformation

EDIT: Structure fixed to correct misdrawn product

[Heory]

I want to make sure wether the two OMe goups were missed by you in the product

[azmanam]

thank you.  yes, the final product should still have the two OMe groups... silly error.  We are not doing a bis demethoxylation.  That would truly be remarkable. Good catch   I've fixed it in the op

[Heory]

I think the you meant 1)Ac2O 2)TsOH

[Dan]

Here's an idea, I haven't really used the TsOH and I have a really dodgy conversion of the hemithioacetal -> ketone in the absence of water (or can I assume the TsOH is the monohydrate?)

[Dan]

Heory, I like your order of reactions better. The ketone formation in yours makes alot more sense than in mine. A couple of things though, I think you lost a carbon when you formed the beta-lactam (should be gamma I think), and your arrows for addition of the enolate to the iminium ion are the wrong way round.

[Heory]

haha. we post almost at the same time. Two very different ways... Insteresting

[Heory]

Oh my god. Yes, dan. I was reviewing chapter of antibotics in my text book this evening which made me think it's a beta-lactam.
correction:

[movies]

I would call the last bit a Pictet–Spengler reaction rather than a Friedel–Crafts.

Also, if you draw a different resonance structure, then the first cycloaddition can be called a Diels–Alder.

[jinclean]

Hello!Dan! i agree with your steps except the sulfur ylide make the addition to the ester group.Heory's 1,3 dipole cycloaddition is more better.but other steps is so excellent! i feel excited about your mechanism.When i read this question,i am wondering why the nucleophlie must attack the same face as the -COOMe?Could you explain it in more details?

[Heory]

Calculated by computer, the trans-substituted lactam has the energy 63kJ/mol more than the cis-substituted one.
I think the cylohexone ring is hard to twist because 3 bonds should be at the same plane due to the aryl ring.

[azmanam]

Heory get's it right this week.  I thought the mechanism might be too ambiguous without the product, but perhaps it was too straightforward with the product given?

I'd also call the cycloaddition a Diels-Alder, but they're just resonance structures of each other, right?  The neutral resonance structure is probably the better resonance contributor, but the dipolar cycloaddition is still a resonance structure.  The reaction is drawn in the papers as a Diels Alder.

This is methodology from the Padwa group as an entry into the Erythrinane family.  Nice work, imho.

http://dx.doi.org/10.1021/jo9716183
http://dx.doi.org/10.1016/0040-4039(95)00574-V

[jinclean]

Hello!Heory,i think the three bonds should be at the same plane,but why the cis lactam is more favor than the trans lactam?